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See Learning objectives and drug list

On Part 1

Interactive lecture with

Vicki Coffin, PhD Questions today.
Pharm at 4 Thursdays
4 Till 6 PM in LLL
before, 2
to 3 X s.

400 com-

See cover of your Basic and Clinical Pharmacology Textbook
The Mu Opioids
Boxed Warning

DURAGESIC® (fentanyl transdermal system) CII contains a high concentration

of a potent Schedule II opioid agonist, fentanyl. Schedule II opioid substances
which include fentanyl, hydromorphone, methadone, morphine, oxycodone, and
oxymorphone have the highest potential for abuse and associated risk of fatal
overdose due to respiratory depression. Fentanyl can be abused and is subject to
criminal diversion. The high content of fentanyl in the patches (DURAGESIC®)
may be a particular target for abuse and diversion. DURAGESIC® is indicated
for management of persistent, moderate to severe chronic pain that: Requires
continuous, around-the-clock opioid administration for an extended period of
time, andCannot be managed by other means such as nonsteroidal analgesics,
opioid combination products, or immediate-release opioids. DURAGESIC®
should ONLY be used in patients who are already receiving opioid therapy, who
have demonstrated opioid tolerance, and who require a total daily dose at least
equivalent to DURAGESIC® 25 mcg/hr. Patients who are considered opioid-
tolerant are those who have been taking, for a week or longer, at least 60 mg of
morphine daily, or at least 30 mg of oral oxycodone daily, or at least 8 mg of oral
hydromorphone daily or an equianalgesic dose of another opioid.

Prescription Drug Misuse

Aberrant Medication-Taking Behaviors (AMTBs)

A spectrum of patient behaviors
that may reflect misuse

Total Chronic Pain Population

Most patients on long-term opioid medications are not addicted.
Past Year Initiation of Non-medical Use of Prescription-type
Psychopharmaceutics, Age 12 or Older: In Thousands, 2002-
New Users (x 1000)

600 Pain Relievers
400 Tranquilizers
200 Stimulants
0 Sedatives
2002 2003 2004 2005 2006 2007 2008

SAMHSA Office of Applied Studies, NSDUH data, 2009

U.S. Rates of Death
from Unintentional
Drug Overdoses
and Numbers of
Deaths, According
to Major Type of

Okie S. N Engl J Med

Do the benefits of this
treatment outweigh the
untoward effects and
risks in this patient or
to society?

NIDA: resource
Helping Patients Who Drink Too Much, 2007.
NIAAA. Clinicians Guide to Helping Patients Who Drink Too Much, 2007.
Smith et al. Alcohol Clin Exp Res, 2007.
Respiratory depression – can lead to death

Nausea & vomiting ~50% of people experience


Constipation– treated with laxatives

Urinary retention– may require catherization

Produces euphoria and at times hallucinations

Opioid tolerance

Physical dependence
Opioid Antagonists
– displace opioids from receptor
but have no intrinsic activity
– Naloxone
Parenteral, IV
Short half-life
Treatment of opioid overdose
– Naltrexone
Longer duration of action
Treatment of opioid addicts,
drug free, highly motivated
Treatment for alcoholism



(extended release)

Fentanyl Therapeutic dose

Naloxone (after administration Overdose
of single dose)

0 4 8 12 24 48 72 96 120

Figure 1. Onset and Duration of Action in Therapeutic Dosing and Overdose of Selected Opioid Analgesic Agents.
I f ti b t th t i ff t f i id l i d ft tb th i d f t th

Symptoms of an overdose of an opioid can happen for

a very long time while the half life of naloxone is
short. Usually have to do repeated doses and monitor
the patient.
these patients are used to IV dose

0 6 12 18 24
Time (hours)
Why Buprenorphine Was Developed?
and when not taking— acts as agonist to avoid withdrawal

Partial agonist properties

blocks rewarding effect
if relapse occurs —
acts as agonist

Slow off-rate from Mu receptor

Limited or non-existent physical
Less toxic than other opiates
Buprenorphine (Blue Line)
partial agonist
at Mu
poor substitute
for heroin high.

High affinity at
the Mu
Addition of Naloxone to Buprenorphine Reduces
Abuse Potential: Special formulation

naloxone wont get through mucosa orally, but buprenorphine will

Naloxone will block buprenorphine s effects by the

IV but not the sublingual route. Not absorbed

Sublingual absorption of buprenorphine

@ 70%; naloxone @ 10%

If injected, BUP/NX will precipitate withdrawal in a

moderately to severely dependent addict. Limits
misdirection to the street.
Amphetamine has
multiple effects on
dopamine and

1. Induce release of
these NTs from
presynatic terminals.
2. and from vesicles
3. Binds to MAO
4. Binds to DA
reuptake sites
Sudden death in cocaine
users 3% in either acute or
chronic users.

81% also had smoked at

the time.

76% have taken alcohol.

This cocktail produces

lesions as if one has
premature heart and CV
Disulfiram – may inhibit dopamine b- hydroxylase, reduces NE
production. Might help curb re-enforcing effects and craving and
increase the aversive effects of cocaine.

Naltrexone- reduce use and craving.

There is a cocaine vaccine which is showing some promise to help

increase abstinence.

Bupropion being tested for methamphetamine addiction treatment.

Need to address the craving and drug seeking behavior.
Conditioned cues are very strong and relapse is high.

Need CBT, psycho social support. Can get positive effects. $$$ can
be a reinforcer.
What’s New

The use of buprenorphine and naltrexone (very

low doses) together for cocaine abuse.
Buprenorphine acts like a partial agonist at mu
opioid receptors and an antagonist at kappa
Dysphoria may be triggered from a
supersensitive kappa system that results from
stimulant abuse and the resultant compulsive
drug seeking behavior that occurs in some
Visual hallucinations


Altered Perceptions
in multiple senses

Flashbacks are
possible after
Signs and Symptoms of
Hallucinogen Intoxication

Marked anxiety and depression

Perceptual changes

Thought disorders

Impaired judgment

Autonomic arousal
Mescaline, active ingredient
How do they work?

Psilocybin – works 1 – 4 hours

LSD – works 1-8 hours
Mescaline – works 10 or more hours
Various effects on 5HT receptors, result is to
decrease 5HT firing and acts as an agonist at some
specific 5HT sub-types. In addition, it has various
agonist, antagonist effects at dopamine sites.
Use benzo’s in the emergency room for panic and
anxiety related to bad trip.
NMDA glutamate
Produce paranoia,
mood shifts, out of
body, agitation,
Teratogenic in
animals, damages
the brain; enhances
TEENs abuse: Dextromethorphan –
D-isomer of Codeine Background

“robo tripping” – tripping on Robitussin
Triple C – Coricidin Cough and Cold
Cough Medicine –suppresses medullary cough center – its an
NMDA antagonist

Euphoria and hallucinations

Lethal dose 50 mg – users 15-20 mg, give naloxone for
overdose if respiratory depression is present
Check liver for acetaminophen overdose
Designer Drugs- Dangerous

Smiles – like Ecstasy or LSD –

hallucinations, panic attacks and seizures
2C-E or Europa – phenethlyamines – LSD
like actions - Schedule 1 drug
“bath salts” – MDPV – stimulant – overdose
K2 – Spice : herbs laced with cannabinoids
and hallucinogens. Hallucinations and panic.
Stay in the body a long time.
Rapid on and off